Staphylococcus aureus infections are associated with considerable morbidity and mortality in hospitals worldwide including the VA Healthcare System. Dr. Schweizer's long term career goal is to develop and evaluate evidence based strategies to reduce the prevalence of and poor outcomes associated with healthcare-associated infections in the VA Healthcare System. The purpose of this application is to provide Dr. Schweizer with opportunities for specific training in comparative effectiveness research, use of national VA databases, mathematical modeling of infectious diseases, and implementation science to assist in her development as an independent VA health services researcher specializing in hospital-associated infection prevention. The objective of this application is to compare the effectiveness of strategies to prevent and treat S. aureus infections. Multiple organization-level and patient-level strategies have been proposed for S. aureus prevention and treatment. Unfortunately, all have advantages and disadvantages, and there is little evidence to support the effectiveness of these strategies. The current literature assessing strategies to prevent S. aureus transmission often lack external validity, thus it is difficult to apply study results to different patient populations. In 2007, th Veterans Health Administration (VHA) Methicillin-resistant S. aureus (MRSA) Prevention Initiative mandated that all VA Medical Centers test the noses of all admitted patients for MRSA and limit contact with MRSA positive patients in order to prevent MRSA spread. However, few studies have compared this strategy to other potential strategies to determine if this is the most effective and cost-effective strategy to reduce transmission. MRSA is an antibiotic resistant form of S. aureus and comprises approximately half of all S. aureus infections. Thus, strategies that aim to prevent both MRSA and methicillin-susceptible S. aureus (MSSA) may be more effective than strategies solely focused on MRSA. Additionally, there is little consensus on the optimal treatment for S. aureus infections. Many physicians prescribe the antibiotic vancomycin for all S. aureus infections although this may not be optimal. The three aims of this research proposal are: 1) Complete a systematic review and meta-analysis of the effectiveness and costs of different organization-level S. aureus infection prevention strategies implemented: a) Among all admitted patients; b) Among patients who are transitioning through the healthcare system; 2) Compare the effectiveness of vancomycin to that of other anti-staphylococcal antibiotics for the treatment of invasive S. aureus (MRSA and MSSA) infections; and 3) Using organization-level and patient-level data collected in Aims 1 and 2, create a decision model to compare the effectiveness, costs, and cost-effectiveness of strategies to prevent and treat S. aureus infections. The VHA has invested considerable time and resources into the prevention of MRSA transmission and infection through the VHA MRSA Prevention Initiative. This study is consistent with the mission of the VHA in attempting to determine the most effective and cost-effective strategies that can be implemented by the VHA MRSA Prevention Initiative to prevent and treat S. aureus (including MRSA) infections. Thus preventing S. aureus related morbidity and mortality among our nation's veterans. This study will utilize a meta-analysis, a large VA retrospective cohort study, and mathematical models to assess the most effective and cost- effective strategies to reduce transmission, infection, and mortality related to S. aureus. These data are integral to the prevention and treatment of S. aureus invasive infections.